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The number of pregnant women with opioid use disorder (OUD) has quadrupled from 1999 to 2014. Current first line treatment for OUD in pregnancy is methadone with increasing support for buprenorphine. Limited data exist on use of buprenorphine/naloxone for OUD in pregnancy despite it being standard therapy in the non-pregnant individuals. The aim of this study was to compare neonatal opioid withdrawal syndrome (NOWS) prevalence and characteristics among neonates born to women prescribed methadone and buprenorphine/naloxone.This is a retrospective cohort analysis of mother-neonate dyads treated with either methadone or buprenorphine/naloxone for OUD in pregnancy who received prenatal care in the substance abuse, treatment, education, and prevention program (STEPP) clinic and delivered at OSU. Primary neonatal outcomes included: neonates diagnosed and treated for NOWS, peak scores on Modified Finnegan Neonatal Abstinence Score (FNAS), number of scores ≥9 on FNAS, and duration of treatment for NOWS. Secondary outcomes included: fetal growth restriction, preterm birth (37 weeks), neonatal head circumference, birth weight, NICU admission, five-minute Apgar score, and length of hospitalization.From 2013 to 2017, we identified 588 mother-neonate dyads: 149 treated with methadone and 439 treated with buprenorphine/naloxone. Ninety-eight neonates (65.8%) in the methadone group were diagnosed with NOWS requiring pharmacological interventions compared with 170 (38.7%) in the buprenorphine/naloxone group (aOR 3.46, 95% confidence interval (CI) 2.31-5.20,Buprenorphine/naloxone treatment for OUD in pregnancy appears safe and has decreased NOWS and pharmacologic intervention for the neonate.

OBJECTIVES To assess the association between aspirin and glycemic control in diabetic, pregnant patients, and the risk for aspirin resistance in those with poor glycemic control across gestation taking low-dose aspirin (LDA) for pre-eclampsia (PEC) prevention. STUDY DESIGN We performed a secondary analysis of samples collected during the Maternal-Fetal Medicine Units trial of LDA for PEC prevention. A subset of insulin-controlled diabetic patient samples on placebo or 60 mg aspirin daily were evaluated. Glycosylated hemoglobin was measured at randomization, mid-second trimester, and third trimester time points. Thromboxane B2 (TXB2) measurements were previously assessed as part of the original study. Primary outcome was the effect of LDA on glycosylated hemoglobin levels compared with placebo across gestation. RESULTS Levels of glycosylated hemoglobin increased across gestation in the placebo group (2,067.7 [interquartile range, IQR: 1,624.6-2,713.5 µg/mL] vs. 2,461.9 [1,767.0-3,209.9 µg/mL] vs. 3,244.3 [2,691.5-4,187.0 µg/mL]; p

Background LDA triggers biosynthesis of endogenous anti-inflammatory molecules, aspirin-triggered 15-epi-lipoxin A4 (15-epi-LXA4), which may counteract inflammatory process of preeclampsia (PE), and play role in LDA’s mechanism of action in PE prevention in high-risk patients. Objective Investigate the effects of daily LDA on levels of 15-epi-LXA4 in pregnancies at high-risk for developing PE. Materials and methods Secondary analysis of multi-centered randomized controlled trial investigating effects of daily LDA (60 mg) in high-risk pregnancies. Maternal samples were drawn at three points: before LDA initiation (13–26 weeks’ gestation), 24–28 weeks’ gestation (at least two weeks after LDA) and 34–36 weeks’ gestation. 15-epi-LXA4 levels were measured by ELISA. Results Analysis included 82 patients: 63 receiving daily LDA and 29 receiving daily placebo starting between 13 and 25 weeks gestation. Prior to randomization, baseline 15-epi-LXA4 levels were similar between both groups (75.9 pg/mL [IQR; 63.8–114.0] vs 136.2 pg/mL [52.4–476.2]; p = 0.10). Patients receiving daily LDA were noted to have significantly increased levels of 15-epi-LXA4 after LDA administration (136.2 pg/mL [IQR; 52.4–476.2] vs 1758.2 pg/mL [905.4–6638.5]; p Conclusion Daily LDA administration increases 15-epi-LXA4 levels in high-risk pregnancies for PE. In LDA group, pregnancies complicated by PE have lower levels of 15-epi-LXA4 compared to pregnancies without PE.

Untreated opioid misuse in pregnancy is associated with adverse outcomes. Limited information is available on maternal and perinatal outcomes in subsequent pregnancies for individuals initiated on medication for opioid use disorder (MOUD) in a prior pregnancy.Evaluate maternal and neonatal outcomes in subsequent pregnancies for individuals initiated on MOUD in prior pregnancy.Historical cohort study including individuals with opioid use disorder with ≥2 pregnancies between 2013 and 2020, received care in our colocated multidisciplinary clinic for1 pregnancy, and delivered at our institution. Primary outcome was rate of preconception MOUD. Secondary outcomes included rate of neonatal opioid withdrawal syndrome requiring pharmacologic treatment and length of hospital stay.Forty-two individuals with opioid use disorder in their index pregnancies (n = 42) and 46 subsequent pregnancies were identified. Individuals were more likely to receive long-acting reversible contraception in subsequent pregnancies (35% vs 14%, P = 0.04). No differences in tobacco use, gestational age at initiation of prenatal care or delivery was noted. Individuals in their subsequent pregnancies were 6 times more likely to be on MOUD preconception (78% vs 36%; OR, 6.48; [95% CI, 2.52-16.64]) and 67% less likely to have positive illicit urine drug screen upon initiation of care (36% vs 64%; OR, 0.33; 95% [CI, 0.14-0.78]). Neonates had similar rates of neonatal abstinence withdrawal syndrome requiring pharmacological treatment, positive illicit toxicology results, and neonatal length of stay.Participation in multidisciplinary obstetric and opioid use disorder program increases rate of MOUD in subsequent pregnancy with decrease in illicit drug use.

Objective Isolated fetal ventriculomegaly is often an incidental finding on antenatal ultrasound. It is benign in up to 90% of cases, although it can be associated with genetic, structural, and neurocognitive disorders. The literature suggests that over 40% of isolated mild ventriculomegaly will resolve in utero, but it is unclear if resolution decreases the associated risks.The aim of this study is to compare the fetal and neonatal genetic outcomes of ventriculomegaly that persists or resolves on subsequent ultrasound. Study Design This is a retrospective cohort study of women diagnosed with isolated ventriculomegaly via fetal ultrasound at a tertiary referral center between 2011 and 2019. Patients were excluded if other structural anomalies were identified on ultrasound. Results A total of 49 patients were included in the study, 19 in the resolved ventriculomegaly group and 30 in the persistent ventriculomegaly group. Women in the resolved ventriculomegaly group were more likely to be diagnosed earlier (24 vs. 28 weeks, p = 0.007). Additionally, they were more likely to have mild ventriculomegaly (63 vs. 84%, p = 0.15), and less likely to have structural neurological abnormalities diagnosed on postnatal imaging (5 vs. 17%, p = 0.384), although these were not statistically significant. Aneuploidy risk for resolved compared with persistent ventriculomegaly was similar (5 vs. 7%, p = 0.999). Conclusion This study suggests that resolution of isolated ventriculomegaly in utero may not eliminate the risk of genetic or chromosomal abnormalities in this population and may warrant inclusion as part of the counselling of these at-risk patients. Larger prospective studies are needed to confirm these findings. Key Points

BackgroundPreeclampsia (PE) is a pregnancy-specific vascular endothelial disorder characterized by multi-organ system involvement. This includes the maternal kidneys, with changes such as continuous vasospasm of renal arteries and reduced renal blood flow. However, it is unclear whether similar renal vascular changes are seen in the fetus. This study sought to compare renal artery impedance in fetuses of women with and without PE.MethodsThis was a prospective Doppler assessment study of the fetal renal artery impedance in 48 singleton fetuses. The group with PE consisted of 24 appropriately grown fetuses in pregnancy complicated by both mild and severe PE and a control group of 24 uncomplicated pregnancies. Doppler studies included renal artery systolic/diastolic (S/D) ratio, pulsatility index (PI), resistance index (RI), and identification of end-diastolic blood flow.ResultsFetuses of mothers with PE were more likely to have a lower renal artery Doppler S/D ratio (7.85 [6.4–10.2] vs. 10.8 [7.75–22.5], P = 0.03) and lower RI (0.875 [0.842–0.898] vs. 0.905 [0.872–0.957], P = 0.03). However, there was no statistically significant difference in PI. There was also no difference in the incidence of absent end-diastolic flow.ConclusionThis study suggests that PE results in changes in blood flow to the renal arteries of the fetus. This may be associated with long-term adverse health effects later in adulthood.

OBJECTIVE Peripartum cardiomyopathy (PPCM) affects 1:1,000 U.S. pregnancies, and while many recover from the disease, the risk of recurrence in subsequent pregnancy (SSP) is high. This study aims to evaluate the utility of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) to predict the risk of recurrence of PPCM in SSP. STUDY DESIGN We retrospectively evaluated outcomes in women with a history of PPCM and SSP at a large-volume cardioobstetrics program (2008-2019). RESULTS There were 18 women who had incident PPCM and pursued SSP. Of 24 pregnancies in these women, 8 (33%) were complicated by the development of recurrent PPCM. LVEF ≥ 52% or GLS ≤ -16 was associated with a low risk of recurrent PPCM. CONCLUSION Approximately one-third of women with PPCM developed recurrent PPCM in SSP. LVEF and GLS on prepregnancy echocardiography may predict the risk of recurrence. Additional studies evaluating risk for recurrence are required to better understand which women are the safest to consider SSP. KEY POINTS · Peripartum cardiomyopathy affects 1:1000 US pregnancies.. · Approximately one third of women with a history of peripartum cardiomyopathy developed recurrent disease in a subsequent pregnancy. · A left ventricular ejection fraction ≥52% or global longitudinal strain ≤-16 on echocardiogram is associated with a low risk of recurrence.

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-associated hepatic disorder characterized by pruritus in the setting of elevated serum bile acids (BA). Risk factors for the disease include preexisting hepatobiliary disease, personal or family history of ICP, and advanced maternal age. Recent data suggests that patients with severe ICP (BA ≥100 μmol/L) have a higher risk of adverse pregnancy outcomes including stillbirth.This was a retrospective cohort study of patients diagnosed with ICP between 2012 and 2019 at a tertiary referral center. ICP was defined as symptomatic pruritus combined with serum BA10 μmol/L. Maternal characteristics and outcomes were abstracted from electronic medical records. Baseline characteristics were compared between patients with mild (BA40 μmol/L), moderate (BA 40-99 μmol/L) and severe (BA ≥100 μmol/L) ICP. Obstetrics and neonatal outcomes for patients in each category were then analyzed. Shapiro-Wilk test was used to test for normality for continuous variables, and ANOVA, Kruskal-Wallis, Chi-squared or Fisher's exact tests were used as appropriate. A438 patients were included in the analysis. Individuals with pregestational diabetes (In patients with ICP, those with pregestational diabetes, history of ICP, prior cholecystectomy, and tobacco use are more likely to develop severe disease. Given the adverse outcomes associated with severe disease, serial BA measurements to monitor for development of severe disease may be warranted in this population.

Problem Limited data exists on the temporal trend of the Sars‐CoV‐2 immunologic response and duration of protection following natural infection. We sought to investigate the presence and duration of Sars‐CoV‐2 serum antibodies in obstetrical healthcare workers (HCW) on serial assessments over a 6‐month period, and to assess rates of vaccine acceptance and reported vaccine side effects among this cohort. Method of study A prospective cohort study of a convenience sample of obstetrical HCWs at a tertiary hospital. Serum Sars‐CoV‐2 antibodies for Immunoglobulin G (IgG) and Immunoglobulin M (IgM) were measured longitudinally at four intervals: baseline, 4 weeks, 12 weeks, and 6 months. Participants completed voluntary surveys on COVID19 testing, high‐risk exposures, vaccine acceptance, and vaccine side effects. Results One hundred twenty‐six of 150 (84%) HCWs who volunteered for participation completed all four blood draws. Prevalence of seropositive HCWs based on positive Sars‐CoV‐2 IgG antibodies increased from 2% at baseline to 31% at 12 weeks but declined to 21% by 6 months. Forty‐two percent (19/43) of the participants considered seropositive for Sars‐CoV‐2 IgG antibodies at any of the initial three blood draws converted to seronegative status at the 6‐month follow‐up. Eighty‐seven percent (72/83) of participants who responded to a follow‐up survey were willing to accept the COVID19 vaccine. Rates of acceptance did not differ by participant antibody status. Those that experienced symptoms with the first injection were more likely to have positive Sars‐CoV‐2 IgG antibodies (36.8% vs. 9.6%, p = .01). Conclusion Sars‐CoV‐2 IgG antibodies wane over time and may not provide prolonged and robust immune protection. This underscores the importance of vaccination and continued research in this area while the COVID19 pandemic continues.

BACKGROUND Pregnancies complicated by hypertensive disease of pregnancy often require labor induction. Rates of cesarean delivery range from 15% to 60% in this population. Nitric oxide deficiency has been shown to underlay the pathophysiology of preeclampsia, and nitric oxide promotes cervical ripening. OBJECTIVE We hypothesized that addition of vaginal isosorbide mononitrate for labor induction could decrease the rate of cesarean delivery in pregnancies with hypertensive disease of pregnancy. STUDY DESIGN This study was a double-blind, placebo-controlled, randomized trial of patients with singleton pregnancy at ≥24 weeks' gestation undergoing labor induction for hypertensive diseases of pregnancy between November 2017 and February 2020. Participants were eligible if their Bishop score was

LDA triggers biosynthesis of endogenous anti-inflammatory molecules, aspirin-triggered 15-epi-lipoxin AInvestigate the effects of daily LDA on levels of 15-epi-LXASecondary analysis of multi-centered randomized controlled trial investigating effects of daily LDA (60 mg) in high-risk pregnancies. Maternal samples were drawn at three points: before LDA initiation (13-26 weeks' gestation), 24-28 weeks' gestation (at least two weeks after LDA) and 34-36 weeks' gestation. 15-epi-LXAAnalysis included 82 patients: 63 receiving daily LDA and 29 receiving daily placebo starting between 13 and 25 weeks gestation. Prior to randomization, baseline 15-epi-LXADaily LDA administration increases 15-epi-LXA

PURPOSE OF REVIEW: To review the rational, biological plausibility, and discuss the current research on novel interventions for the prevention of preeclampsia. RECENT FINDINGS: Preeclampsia affects up to 8% of pregnancies worldwide and remains a major cause of maternal and neonatal morbidity and mortality. Multiple medications have been investigated or repurposed as potential effective interventions for preeclampsia prevention. Aspirin is currently the only drug for which there is some evidence of benefit for preeclampsia prevention, and its use is recommended by professional societies for pregnancies at risk. Statins have shown promise for prevention of preeclampsia in animal models and human pilot studies, without any trend or concerns for safety signals or teratogenicity. The use of metformin has also gained popularity in experimental studies but observations from randomized clinical trials were not consistent on its utility as a possible intervention for preeclampsia prevention. While initial studies evaluating esomeprazole were promising, randomized trials failed to show benefit. SUMMARY: Contemporary research shows exciting new opportunities for prophylactic treatment for preeclampsia, to prevent this debilitating and life-threatening disease.

To investigate the association between meconium-stained amniotic fluid (MSAF) and postcesarean surgical site infections.This was a secondary analysis of the Maternal-Fetal Medicine Units Network (MFMU) Cesarean Registry. Women with a singleton pregnancy attempting labor or induction of labor, who ultimately had a cesarean delivery, were included in the study. Pregnancies complicated by MSAF (A total of 18,112 patients were included in the study. 4262 (38%) had meconium-stained amniotic fluid. After accounting for potential confounders in a multivariable logistic regression, meconium-stained amniotic fluid was associated with an increased risk of postoperative surgical site infection (odds ratio 1.16, 95% CI 1.03-1.30).Meconium-stained amniotic fluid may be associated with an increased risk of postoperative surgical site infection.

OBJECTIVE To investigate whether women using intravaginal progesterone suppositories for preterm birth prevention during pregnancy will have lower rates of group B streptococcus (GBS) colonisation at term, compared with women receiving intramuscular 17-alpha-hydroxyprogesterone caproate. DESIGN This was a retrospective observational cohort study of women who were prescribed a progestogen during their pregnancy for preterm birth prevention, and who delivered at term. SETTING A tertiary referral hospital in central Ohio. POPULATION Patients who were prescribed a progestogen during their pregnancy for preterm birth prevention between 2004 and 2017 were included in the study. Patients who delivered at

Preeclampsia is an obstetric disorder that affects 3–8% of pregnant women and remains a leading cause of short- and long-term neonatal and maternal morbidity and mortality. Professional societies recommend the use of low dose aspirin to prevent preeclampsia in high-risk women. However, interest in prevention of this disease and better understanding of its pathophysiology have led to growing research on other agents. This review focuses on the main therapeutic agents evaluated or in use for preeclampsia prevention.

Cervical cancer is the 2nd most common female cancer worldwide. However, in the developed world, cervical screening has reduced this cancer burden. Most smear referrals are low-grade, requiring continuous monitoring until they regress. Others need monitoring for static disease, while a few require treatment due to persistent low-grade or progressive disease. The ‘Holy Grail’ in cervical screening is predicting which patient is likely to have progressive disease. Fourier-transform infrared (FTIR) spectroscopy exploits the fact that an infrared (IR) spectrum represents a “biochemical-cell fingerprint”, which can be obtained from a cellular specimen based on a wavenumber-dependent absorption band pattern of constituents' vibrating chemical bonds. Low-grade (CIN1) specimens (n = 67) diagnosed on cytology were analysed using IR spectroscopy. The n = 67 study participants were rescreened by conventional cytology after a year whereupon three showed progressive disease and 31 had persistent low-grade atypia; 33 had regressed. Spectra from the initial cytology samples were then analysed using principal component analysis (PCA) with output (10 principal components) being inputted into linear discriminant analysis (LDA) to predict which samples would progress, remain static or regress; this approach was compared with variable selection techniques, namely the successive projection algorithm (SPA) and genetic algorithm (GA). Significant wavenumbers distinguishing regressive vs. static disease were 1736 cm−1, 1680 cm−1, 1512 cm−1, 1234 cm−1, 1099 cm−1 and 968 cm−1; separating the two categories is difficult due to a significant degree of ‘overlap’. Progressive disease can be significantly differentiated from static disease based on wavenumbers 1662 cm−1, 1648 cm−1, 1628 cm−1, 1512 cm−1, 1474 cm−1 and 965 cm−1; it can be segregated from regressive disease with 1686 cm−1, 1674 cm−1, 1625 cm−1, 1561 cm−1, 1525 cm−1 and 1310 cm−1. The GA–LDA model shows good separation for all categories (i.e., regressive vs. static vs. progressive disease) using 35 wavenumbers. An ability to predict progressive disease will reduce the need for repeat smears every six months whilst allowing early identification of patients who require treatment.

Background: The umbilical coiling index (UCI) is a measure of the number of coils in the umbilical cord in relation to its length. Hypercoiled cords with a UCI of >0.3 coils/cm have been associated with adverse fetal and neonatal outcomes. Aims: The primary aim is to determine the accuracy of UCI measured on second trimester ultrasound in predicting UCI at birth. The secondary outcome is to investigate the association between hypercoiling of the umbilical cord on prenatal ultrasound and adverse maternal, fetal and neonatal outcomes. Methods: This was a prospective cohort study of uncomplicated singleton pregnancies. Seventy two patients were included in the study. UCI was measured in the second trimester ultrasound, and compared to UCI measured postnatally. Outcomes of patients with hypercoiled cords on ultrasound were compared to outcomes of patients with normocoiled cords. Results: Our results failed to show a strong correlation between the UCI determined with ultrasound, and the UCI determined with examination of the umbilical cord after delivery. We also did not demonstrate that measurement of the UCI on second trimester ultrasound is able to predict adverse maternal, fetal or neonatal outcomes. Conclusion: This study suggests that measurement of the umbilical coiling index should not be part of routine second trimester sonography in patients with uncomplicated singleton pregnancies, with no other medical or surgical comorbidities.

This is a case of a rapidly enlarging cutaneous pedunculated tumor on a patient’s thumb during her pregnancy. This was excised and identified as a hemangioma. A literature search identified a possible hormonal factor in causing an accelerated growth of this tumor.

A 40-year-old Caucasian male presented to the Emergency Department complaining of intermittent painless frank haematuria. Past medical history was significant for Hereditary Non-Polyposis Colon Cancer (HNPCC) and a prophylactic total colectomy. Computed tomography urogram showed thickening in the posterior wall of the bladder. Cystoscopy showed a small bladder mass. Histology showed a papillary urothelial neoplasm of low malignant potential. HNPCC, also known as Lynch Syndrome, is an autosomal dominant disorder responsible for 3-5% of colorectal cancers. There are certain cancers known to be associated with HNPCC; colorectal cancer, endometrial, ovarian, stomach, pancreas, biliary tract, small bowel, brain, renal pelvic and ureteric tumours, sebaceous gland adenomas and keratocanthomas. An association with bladder tumours is not well established.

This retrospective cohort study examined 143/39,895 (0.36%) consecutive born-before-arrival (BBA) births. The incidence of BBA births doubled from 0.26% in 2005 to 0.5% in 2009. This increase was mainly attributed to the increase of non-Irish nationals and patients from low socioeconomic groups attending for antenatal care. Poor social background was often coupled with current or past substance misuse and/or a diagnosis of an infectious disease. While there was no excess in maternal morbidity, the perinatal mortality rate among BBA births was three-fold increased (27.9/1,000) when compared with the overall rate for all inborn babies in our hospital (8.5/1,000) but significantly less than previously published (58.4/1,000). Results of our study call for continuing training of paramedic staff involved in these deliveries and neonatal resuscitation. Given the easy accessibility of antenatal services in Ireland, this study highlights the urgent need for optimising parental education and care in this vulnerable group of patients.

The unplanned nature of kidney transplantation necessitates that patients undergo surgery without prior cessation of warfarin. Our study analyses the impact of warfarin treatment in the peritransplant period on graft outcome and perioperative transfusion requirements.We identified 31 patients undergoing deceased donor kidney transplantation who were concurrently receiving warfarin therapy, between 2000 and 2008. A random, sex-matched, adult, deceased donor control group of 62 patients was generated from the Irish transplant database.The warfarin group were older (mean 47.5 vs. 42.5 years, p=0.067) and had spent longer on dialysis prior to transplantation (mean 3.5 vs. 2.1 years, p=0.004). Graft survival in the warfarin group was not significantly different at 1-, 3- and 5-year follow-ups. There was no statistically significant difference in red blood cell transfusions between the groups (45% vs. 29%, p=0.2). Warfarin patients had a prolonged mean cold ischaemia time (22.3 vs. 18.5 hours, p=0.002).This study demonstrates excellent short- and long-term results for kidney transplantation in patients requiring warfarin at the time of transplantation.